Maternal cocaine abuse is a significant public health issue particularly affecting children, with high rates of reported abuse, neglect and foster care placement. However, little is known about how cocaine exposure affects brain circuits involved in maternal behavior, especially in humans. Functional MRI studies have shown that in mothers, infant cues activate similar brain reward circuits to cocaine, suggesting common dopaminergic pathways. Maternal behavior is strongly influenced my oxytocin, an important neuromodulator and hormone, which may also be modulated by maternal cocaine abuse. Thus, natural infant-related reward stimuli and artificial stimulants such as cocaine may differentially affect neural development, affecting both dopaminergic and oxytocin systems. In this project we test whether maternal responses to infant cues are impaired in cocaine exposed new mothers, using 1) functional MRI and 2) videotaped mother-infant interaction. We hypothesize that cocaine exposed mothers will show significantly less activation of the prefrontal cortex and reward-associated brain regions, on viewing pictures of their own baby's face and cry cues vs. an unknown baby, compared to controls. Specific regions of interest will include the mesocorticolimbic dopamine circuits (ventral tegmental area, ventral striatum and medial prefrontal cortex) and the nigrostriatal regions (substantia nigra, dorsal striatum and dorsolateral prefrontal cortex). 400 mothers from 2 study sites (Baylor College of Medicine and Yale Child Study Center) will be enrolled (200 cocaine exposed and 200 control mothers), along with their 6 to 7 month old infants, to participate in three study visits over a three month period. During Visit 1, mothers will complete the Adult Attachment Interview to explore their own childhood experience and attachment patterns. At Visit 2, mothers will participate in a free play interaction with their infant, which will be videotaped and coded. At the final study visit, functional MRI will be used to compare maternal brain responses to infant facial and cry cues, comparing own infant vs. unknown infant cues. Ultimately, this research may lead to a better understanding of how adverse early life experiences may contribute to adult patterns of caregiving, as well as susceptibilities to addiction, which may further impair parenting capacities. Understanding how cocaine exposure interacts with other environmental factors to influence maternal behavior may help us both to better respond to addiction, and prevent long-term consequences in children-which may itself include an increased vulnerability to addiction. PUBLIC HEALTH RELEVANCE: Maternal cocaine abuse is a significant public health issue in the United States, with long-lasting implications for families, their children and society, which bears much of the cost for future educational and medical services. This project aims to help us better understand how a mother's responses to her infant may be affected by cocaine use - looking at brain, behavioral and hormonal effects. Understanding how early life experiences may lead to cocaine abuse may also help us to prevent problems for the generation to come.